alkahest (paracelsus, 1491-1541): context and strategy · 2019-04-05 · -alkahest (paracelsus,...
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The InBioSynSolv Project
Virtual laboratory for synthons and biosolvent design based on reverse
molecular engineering
Financing: French ANR program CP2D 2009
Colloque ANR Chimie Durable - Lyon 19 sept. 2012Colloque ANR Chimie Durable - Lyon 19 sept. 2012
The InBioSynSolv Project
• Accreditation by the pôles de compétivitité AXELERA, MAUD• 4 years project : 01/10/2009 – 30/09/2013• total budget: 2.9 M€ / 1.2 M€ financed
Computer and product modeling
Solvent chemistry and formulation
Agro-sourced solvents
Solvents and applicationsInBioSynSolv
leader
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Context and strategy
Designing green « alkahests »
Top-down vs bottom-up approaches
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In Silico design of « green alkahests »
- Alkahest (Paracelsus, 1491-1541): • hypothetical universal solvent, having the power to d issolve
every other substance.
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Bio-solvents
Propertyrequirements
Primary functionSecondary
EEHS-related
IN
glycérolfructose
omega3
Synthons & Building blocks
Plants
IN
Reverse formulation
« clean » ecosynthesis
Life cycle assessment
OUT
Molecules & mixtures
InBioSynSolv
air
waterhealth
food
constraints IN
REAChregulation
price
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Profile of an ideal green solvent
- Major environmental and economic criteria• Non-VOC:
• Pvap < 10 Pa (Europe) or Eb > 250°C (USA)
• Low toxicity to humans and environment: • Non-CMR, biodegradable
• High flash point: • Considered as « non flammable » when Flash Point > 55 °C
• Reasonable price: • 0.5 to 20 €/kg for high value applications
• Synthesized from bio-sourced building blocks not co mpeting with food resources
- Major physico-chemical and process properties• High solvency power• Easy to recover and regenerate at the end of the pr ocess • Miscible to water for some applications
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The InBioSynSolv strategy
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TO
P-D
OW
N A
PP
RO
AC
H
Bio-sourced building-blocks
Bio-sourcedsolvents candidates
Physico-chemical properties
Mp : -66,7 °CPvap : 20 PaBp : 351 °C
δD : 18 MPa1/2
δP : 08 MPa1/2
δH : 14 MPa1/2
Target functionalproperties
Liquid Solvent for dyes, lacquers, pharmaceuticals…
Non VOC,Non CMR
BO
TT
OM
-UP
AP
PR
OA
CH
Relevant chemicaltransformations
Mathematicalmodels
Prediction of functional properties
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Finding renewable resources pools
Synthons or raw biomass?
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Bio-sourced synthons
- Use of synthonsrather than raw biomass
• more reliable, and less variable
- Some results:• 10 main pools of
renewable resources have been identified from the literature
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(Angew. chem. Int. Ed. 2007)
OilsRaw mat.
Synthesissteps
End product
Synthons
End product
End product
Synthons
Biodieselraw mat.
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The Bottom-Up approach: In-silico guided synthesis of green solvents
Finding of renewable resources pools
Relevant eco-friendly chemical transformations
Automatic generation of possible molecules
A posteriori evaluation of the molecules performance
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the Bottom-Up approach
- Relevant eco-friendly chemical transformations
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Bibliographical sources:
���� Synthesis of petrochemical commodities
���� Transformations of bio-based molecules
���� Synthesis of pharmaceuticals
> 500 reactions
have been found
Selection criteria of relevant transformations:
���� Efficiency (good yields)
���� Mild conditions (temperature, pressure)
���� Greenness (atom economy, safe reactants)
���� Cost effectiveness
���� Validation by Rhodia
relevant chemical transformations
the Bottom-Up approach
- Computer aided synthesis ���� the GRASS program• GeneRator of Agro-based and Sustainable Solvents
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Building block
Relevant ChemicalTransformation
Co-reactant
Systematic & flexible approach to generate thousand s of virtual derivatives from any pre-defined buildin g block
Virtual Derivatives
The Top-Down approach
Computer Aided Product Design: Finding molecules that match target properties
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top-down CAPD
- Computer Aided Product Design ���� IBSS Software tool• Set a priori target values for many properties and find / build
candidate molecules and mixtures that satisfy them
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Property models Target
properties
Target
properties
Building
blocks
Building
blocks
Mixture buildingMixture building
Process model
Group contribution 1er order
Molecular descriptors
-CH2, -OH, -NO2, …
-C, -N, -O-, =C, …
Chemical
fragments &
database
Set of molecule /
mixture candidates
Check performanceCheck performanceGenetic algorithm
Objective function
top-down CAPD
- Computer Aided Product Design
���� the IBSS Software tool• Software engineering
• UML2• Component/object oriented
architecture• C#, Java
• XML Standard input files
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Man-Machine Interface
Building Blocks
DatabaseSearchcomponent (IBSS)
PropertyCalculation Model
Library
Activity process in IBSS
top-down CAPD
- Matching the bio-sourced challenges• Customize the properties• Customize the mixture structure
• Molecules• Composition
• Customize the molecule structure• Fragments
– e.g. from renewable pools
• Building blocks– Compliant with sustainability
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a.i. solventwater scentmolecule
composition 5% y%10%<x<30% <2%
Building
blocks
Chemical
groups
built from
built from
Molecule Fragment
Specified Free Specified Free
Performance evaluation
Global performance index
Solvent power
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Performance: global index
- Property • Estimation models • Relative weights
- Performance calculation• Select a performance
function for each property
• near
• above
• below
• Global index: max perf(M)
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Property name Weight Target Mixture Model
Pure Compound Model
Molecular weight 1 <200 g/mol
Flash point 1 >323.15K linear Catoire 2006
Vapor pressure 1 <0.00267 bar linear Riedel, 1954
RED 4 <0 Non linear HSPiP
Env.Waste 0.2 >8 linear Weis, 2009
Env.Impact 0.2 >8 linear Weis, 2009
Health 0.2 >8 linear Weis, 2009
Safety 0.2 >8 linear Weis, 2009
LCA 0.2 >8 linear Weis, 2009
Viscosity (300K) 1 [0.8;1.4] cp Tamura 53 Conte, 20 08
Surface tension@298K 1 [30;45] dyn/cm2 Teja & Rice Conte, 2008
Density 1 [0.9;1.1] linear HSPiP
Log(Ws) 4 >4 mg/L linear MG 2002
Finding an aqueous solvent to wash blanket ink
Performance: solvent power
- Hansen Solubility parameter• Split of Hildebrand δδδδ into:
• δδδδ D dispersive contribution • δδδδ P polar contribution• δδδδ H H-bond contribution
• Principle• The closer the HSP of two
materials, the more likely it is that they have higher affinity than had their HSP been farther apart
• Solvents • within the sphere should solubilize
the solute• The closer to the center, the better
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δδδδD
δδδδP
δδδδH
http://www.hansen-solubility.com/index.php
Performance: solvent power
- COSMO σσσσ-potential curves of typical solvents
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σσσσ (e/nm2)
µµµµ
Hexane
Non H+ donorNon e - donor
Water
Atypical profile in the middle=> Lipophobicity
Acetone
e- donor Slightly H + donor
Chloroform
Pyridine
Very good e - donor
Trifluoroethanol
Very good H + donorSlightly e - donor
Examples
Application to glycerol
Augeo SL191®, an industrial new solvent
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Green building-block
Co-reactants
pre-defined chemical
transformations
+ GRASS
Glycerol derivatives
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75 435« Bio-sourced
Potential Derivatives »-ols, acids, -ones, etc..
30977
21562
83834722
4211
33662214
All simple derivatives of glycerol reported on the literature
have been found by GRASS within 5 generations
Glycerol derivatives
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Glycerol derivatives
- Bottom-Up: GRASS• Performance index
- Top-Down: CAPD• Generations
• > 1.3 Millions structures from10 renewable pools
• Performance• > 1000 structures with
performance index > 0.99
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100%
30977
21562
83834722
4211
33662214
Low evaporation rate solvents
remain at the final step. They are
responsible for the leveling of the
film assuring the quality of the film.
Glycerol cetal AUGEO SL 191
- AUGEO application: car refinishing
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- AUGEO SL 191 a new industrial glycerol-based solven t
HO OH
OH H+
HO OO
O+
Solketal(= Augeo SL191®)
73% of the molecule weight comes from a renewable source(could be 100% with bio-acetone)
Brent
Phenol
Acetone
Soya
Biodiesel
Vegetal Oil
Natural Gaz Methanol
glycerolPinhão Manso
Colza
Co-product
Co-product
AUGEO SL 191
Glycerol cetal AUGEO SL 191
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ENVIRONMENTAL PROPERTIES
• Biodegradabillity Not readily biodegradable
• Bio-accumulation Not likely to bioaccumulate
• Acute aquatic toxicity Not classified
• Chronic aquatic toxicity Not classified
TOXICOLOGICAL PROFILE
• Acute toxicity Not classified
• Skin corrosion / irritation Not classified
• Serious eyes damage / irritation Category 2A*
• Respiratory / Skin sensitization Not sensitizing
• Germ Cell Mutagenicity Not classified
• Carcinogenicity Not classified
• Reproductive Toxicity Not classified
SAFETY
• Boiling point 183°C-191 °C• Flammability Category 4• Flash Point (closed vessel) 91°C (combustible)
*Category 2A means that AUGEO SL 191 is irritating to eyes with reversible effects
Glycerol cetal AUGEO SL 191
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- AUGEO: Substitute for glycol ethers in paints and varnishes
OOHO
Boiling Points 189 °C 190 °C
σσσσ-Potential curves
-1,2
-1,0
-0,8
-0,6
-0,4
-0,2
0,0
0,2
0,4
0,6
-3 -2 -1 0 1 2 3
HO
OO
C1P2 and Augeo SL191 exhibit similar evaporation rates and solvency properties
Glycerol cetal AUGEO SL 191
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- AUGEO application: car refinishing
Solvents Boiling Point °C Composition %
Ethyl Acetate 77 18Ethanol 79 57
Isopropanol 82 15Butanol 118 5Solketal
(Augeo SL 191) 189 0
Dipropylene Glycol Monomethyl Ether 190 5
• Similar application results:
• Same evaporation kinetic of the solvent blend
• Same solubility power all along the drying
• Same paint film caracteristics (gloss, adhesion,
chemical resistance…)
• With better tox/ecotox at a comparable price
Glycerol cetal AUGEO SL 191
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InBioSynSolv conclusions
- Main result: • Combine in silico tools
• bottom-up (GRASS oriented synthesis tool)• top-down (CAMD – reverse engineering)
• The cooperative effect• No single partner can provide the solution alone
– Chemist expert – Industrial expert – Modeling expert
» Chemical engineering» Computer engineering
• Publications:• 1 art., 4 art. in prep., 13 proceedings • patents on chemicals in prep.• GRASS and IBSS software : non patentable
– IBSS property library component : licence to
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Thank you for your attention!
Acknowlegments
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Alchemists searching for green ALKAHESTS